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Nuclear DNA damage during NAD(P)H oxidation by membrane redox chains

A V Peskin1

  • 1Institute of Developmental Biology, Russian Academy of Sciences, Moscow.

Free Radical Biology & Medicine
|January 1, 1996
PubMed
Summary

NAD(P)H-dependent redox chains cause nuclear DNA damage via active oxygen species. Iron chelators like EDTA-Fe3+ significantly degrade DNA, with catalase protecting against this damage.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Toxicology

Background:

  • NAD(P)H-dependent redox chains generate active oxygen species.
  • Oxidative stress can lead to nuclear DNA damage.

Purpose of the Study:

  • To investigate nuclear DNA damage induced by NAD(P)H oxidation in the presence of iron chelators.
  • To identify the reactive oxygen species involved in this DNA damage process.

Main Methods:

  • Incubation of isolated rat liver nuclei with NAD(P)H and various iron chelators.
  • Analysis of nuclear DNA damage using alkaline agarose gel electrophoresis.
  • Assessment of the role of superoxide dismutase (SOD) and catalase.

Main Results:

  • EDTA-Fe3+ and DTPA-Fe3+ with NAD(P)H caused significant high molecular weight DNA decay.
  • Catalase, but not SOD, protected against NAD(P)H-induced DNA damage.
  • Cumene hydroperoxide with EDTA-Fe3+ induced DNA damage, enhanced by NADPH.

Conclusions:

  • Nuclear DNA damage occurs during NAD(P)H oxidation with specific iron chelators.
  • Both hydroxyl and alkoxyl radicals are implicated in this DNA damage.
  • These findings suggest a role for membrane redox chains in mediating iron chelator-induced DNA damage.

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